1059Expanded immunogenicity of high-dose inactivated influenza vaccine compared to standard-dose inactivated influenza vaccine in older adults

Abstract

Background: previous studies have demonstrated the superior immunogenicity of high-dose inactivated influenza vaccine (IIV-HD) in older adults compared to standard-dose inactivated influenza vaccine (IIV-SD), as measured by hemagglutination inhibition (HAI) antibody titers against egg-propagated vaccine antigens. The 2012-2013 northern hemisphere influenza season was characterized by high H3N2 activity and by mismatch between predominant circulating strains and egg-propagated vaccines. There is growing interest in evaluating influenza vaccine immune responses beyond the traditional HAI assay. Methods: samples collected as part of a randomized controlled trial (NCT01427309) evaluating the efficacy of IIV-HD vs IIV-SD in adults ≥65 years were available for testing; one third of trial participants provided post-vaccination sera. This sub-study utilized a case-cohort design, in which 675 representative samples collected during the 2012-2013 season of the study (from individuals who either developed polymerase chain reaction/culture confirmed H3N2 influenza illness [N=123] or belonged to a random subset of 10% of non-cases [N=552]) were selected for expanded testing. Expanded immunogenicity was assessed with an HAI assay using an MDCK cell-propagated A/ Victoria/361 (H3N2) antigen, a viral neutralization assay (NT) using both eggand cell-propagated A/Victoria/361 (H3N2) antigens, and an enzyme-linked lectin assay (ELLA) for anti-neuraminidase (N2) antibodies. Geometric mean titers (GMT) were estimated for IIV-HD and IIV-SD recipients using weighted averages and were compared as GMT ratios (IIV-HD/IIV-SD). Results: samples from 318 IIV-HD and 357 IIV-SD recipients were assayed. The GMT ratios (and 95% Confidence Intervals) were 1.48 (1.26; 1.73), 1.53 (1.29; 1.82), 1.75 (1.43; 2.15), and 1.42 (1.23; 1.65) for cell-propagated HAI, egg-propagated NT, cell-propagated NT, and N2-ELLA, respectively. The GMT ratio for the full immunogenicity subset (2879 IIV-HD and 2872 IIV-SD recipients) assessed by HAI assay using egg-propagated A/Victoria/361 was 1.82 (1.71; 1.94). Conclusion: IIV-HD is associated with significantly improved immunogenicity compared to IIV-SD in older adults as assessed using a range of different assays. BACKGROUND • Adults ≥65 years of age are particularly vulnerable to influenza-associated complications, accounting for most seasonal influenza-related hospitalizations and deaths1,2 • The high burden of influenza in this population persists despite documented improvements in vaccination rates3 • An unmet medical need is therefore recognized for improved influenza vaccines in adults 65 years of age and older4,5 • Previous studies have demonstrated the superior immunogenicity of high-dose inactivated influenza vaccine (IIV-HD) in older adults compared to standard-dose inactivated influenza vaccine (IIV-SD), as measured by hemagglutination inhibition (HAI) antibody titers against egg-propagated vaccine antigens6,7,8 • A recently completed randomized, controlled efficacy study demonstrated that IIV-HD was 24.2% (95% confidence interval [CI], 9.7%–36.5%) more efficacious than a IIV-SD in preventing laboratory-confirmed symptomatic influenza in adults 65 years of age and older9 • The second year of the efficacy study (2012-2013 northern hemisphere influenza season) was characterized by high H3N2 activity and by mismatch between predominant circulating strains and egg-propagated vaccines such as the ones used in the study. In contrast, cell-propagated vaccine antigens were considered well-matched to circulating H3N2 viruses10,11 • Consistent with previous studies, the immunogenicity of IIV-HD was significantly improved compared to IIV-SD as determined by the standard HAI assay using egg-propagated vaccine antigens in the full Year 2 immunogenicity subset (2879 IIV-HD and 2872 IIV-SD recipients), with a corresponding GMT ratio of 1.82 (95% CI 1.71; 1.94)9 Figure 1. HAI (Egg-propagated) G M T 0 100 200 300 400 500 600 IIV-HD IIV-SD IIV: inactivated influenza vaccine; HD: high-dose; SD: standard-dose GMT: Geometric Mean Titers; HAI: Hemagglutination inhibition; Error bars represent 95% confidence intervals • There is growing interest in evaluating influenza vaccine immune responses beyond the traditional HAI assay.12 OBJECTIVES • To compare the immunogenicity of IIV-HD vs IIV-SD in adults ≥65 years of age against the A/Victoria/361/2011 (H3N2) influenza virus using methods other than the HAI assay based on egg-propagated antigens.